EP2399620B1 - Implant et son procédé de fabrication - Google Patents

Implant et son procédé de fabrication Download PDF

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Publication number
EP2399620B1
EP2399620B1 EP11168168.0A EP11168168A EP2399620B1 EP 2399620 B1 EP2399620 B1 EP 2399620B1 EP 11168168 A EP11168168 A EP 11168168A EP 2399620 B1 EP2399620 B1 EP 2399620B1
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EP
European Patent Office
Prior art keywords
weight
concentration
implant
iron
minor constituent
Prior art date
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Not-in-force
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EP11168168.0A
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German (de)
English (en)
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EP2399620A3 (fr
EP2399620A2 (fr
Inventor
Ullrich Bayer
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Biotronik AG
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Biotronik AG
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Publication of EP2399620A3 publication Critical patent/EP2399620A3/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22D—CASTING OF METALS; CASTING OF OTHER SUBSTANCES BY THE SAME PROCESSES OR DEVICES
    • B22D7/00—Casting ingots, e.g. from ferrous metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00—Working by laser beam, e.g. welding, cutting or boring
    • B23K26/36—Removing material
    • B23K26/38—Removing material by boring or cutting
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D1/00—General methods or devices for heat treatment, e.g. annealing, hardening, quenching or tempering
    • C21D1/26—Methods of annealing
    • C21D1/30—Stress-relieving
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D8/00—Modifying the physical properties by deformation combined with, or followed by, heat treatment
    • C21D8/06—Modifying the physical properties by deformation combined with, or followed by, heat treatment during manufacturing of rods or wires
    • C21D8/065—Modifying the physical properties by deformation combined with, or followed by, heat treatment during manufacturing of rods or wires of ferrous alloys
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D9/00—Heat treatment, e.g. annealing, hardening, quenching or tempering, adapted for particular articles; Furnaces therefor
    • C21D9/08—Heat treatment, e.g. annealing, hardening, quenching or tempering, adapted for particular articles; Furnaces therefor for tubular bodies or pipes
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/002—Ferrous alloys, e.g. steel alloys containing In, Mg, or other elements not provided for in one single group C22C38/001 - C22C38/60
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/04—Ferrous alloys, e.g. steel alloys containing manganese
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/24—Ferrous alloys, e.g. steel alloys containing chromium with vanadium
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/38—Ferrous alloys, e.g. steel alloys containing chromium with more than 1.5% by weight of manganese
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/60—Ferrous alloys, e.g. steel alloys containing lead, selenium, tellurium, or antimony, or more than 0.04% by weight of sulfur

Definitions

  • the present invention relates to an implant, in particular an intraluminal endoprosthesis whose body comprises at least predominantly a material with the main component iron, as well as a method for producing a corresponding implant.
  • implants are endovascular prostheses or other endoprostheses, for example stents, in particular wire mesh stents, fastening elements for bones, for example screws, plates or nails, intramedullary nails, spiral bundle nails, Kirschner wires, wires for septumoklux, surgical suture, intestinal staples, Vascular clips, prostheses in the hard and soft tissue and anchor elements for electrodes, in particular pacemakers or defibrillators to understand.
  • stents in particular wire mesh stents
  • fastening elements for bones for example screws, plates or nails, intramedullary nails, spiral bundle nails, Kirschner wires, wires for septumoklux, surgical suture, intestinal staples, Vascular clips, prostheses in the hard and soft tissue and anchor elements for electrodes, in particular pacemakers or defibrillators to understand.
  • stents are used more often as implants, which are used for the treatment of stenoses (vasoconstriction). They have a body in the form of a possibly perforated tubular or hollow cylindrical lattice which is open at both longitudinal ends. The tubular grid of such an endoprosthesis is inserted into the vessel to be treated and serves to support the vessel. Stents have become established especially for the treatment of vascular diseases. By using stents narrowed areas in the vessels can be widened, resulting in a lumen gain.
  • stents or other implants can provide an optimal vascular cross-section which is primarily necessary for successful therapy, the persistent presence of such a foreign body initiates a cascade of microbiological processes leading to a gradual stunting of the stent worst case can lead to a vascular occlusion.
  • One approach to solving this problem is to make the stent or other implants from a biodegradable material.
  • Biodegradation is understood to mean hydrolytic, enzymatic and other metabolism-related degradation processes in the living organism, which are primarily caused by the body fluids which come into contact with the biodegradable material of the implant and lead to a gradual dissolution of the structures of the implant containing the biodegradable material.
  • the implant loses its mechanical integrity at a given time through this process.
  • biocorrosion is often used.
  • bioresorption covers the subsequent absorption of the degradation products by the living organism.
  • Materials suitable for the body of biodegradable implants may include, for example, polymers or metals.
  • the body can consist of several of these materials.
  • the common feature of these materials is their biodegradability.
  • suitable polymeric compounds are polymers from the group of cellulose, collagen, albumin, casein, polysaccharides (PSAC), polylactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D, L-lactide co-glycolide (PDLLA-PGA), polyhydroxybutyric acid (PHB), polyhydroxyvaleric acid (PHV), polyalkylcarbonates, polyorthoesters, polyethylene terephthalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and their copolymers, and hyaluronic acid.
  • PSAC polysaccharides
  • PLA polylactide
  • PLLA poly-L-lactide
  • PGA polyglycol
  • the polymers may be present in pure form, in derivatized form, in the form of blends or as copolymers.
  • Metallic biodegradable materials are predominantly based on alloys of magnesium and iron.
  • the present invention preferably relates to implants whose body consists at least predominantly of a biodegradable material with the main component iron, in particular an iron-based alloy (hereinafter also referred to briefly as: iron alloy).
  • the aim is the degradability according to the desired therapy or the application of the respective implant (coronary, intracranial, renal etc.).
  • one important target corridor is that the implant loses its integrity over a four-week to six-month period.
  • integrity ie mechanical integrity
  • the implant is still mechanically so stable that, for example, the collapse pressure has dropped only slightly, ie at most to 80% of the nominal value.
  • the implant can thus still fulfill its main function of ensuring the permeability of the vessel, if its integrity is present.
  • integrity may be defined by the implant being mechanically stable enough to undergo little geometric change in its loading state in the vessel, for example, not collapse significantly, ie, at least 80% of the dilation diameter under load, or in the case of a stent Has barely begun supporting struts.
  • Implants with an iron alloy are particularly inexpensive and easy to produce.
  • these implants lose their mechanical integrity or supportive effect only after a relatively long period, i. only after a stay in the treated organism of about 2 years. This means that the collapse pressure on iron implants for this application will decrease too slowly over time.
  • a long residence time of implants can cause complications in the further treatment of the patient, namely, for example, if the implant in resolution due to its ferromagnetic properties does not allow the study of the patient treated in the magnetic resonance tomograph or too strong influence. Furthermore, a presence of the stent in the vessel wall beyond the necessary residence time there can lead to mechanical irritations, which in turn result in a re-narrowing of the treated vessel. Furthermore, in the case of orthopedic implants (eg bone plates), the formation of new bone substance can lead to mechanical stresses between the slowly degrading implant and the new bone substance. This produces bone deformities or malformations, especially in children and adolescents. It is for such applications therefore desirable if the field of use of implants whose body at least predominantly has a material with the main component iron, could be extended by faster degradation.
  • Implants which are degradable in vivo by corrosion.
  • the material of the known implants contains iron as the main component as well in a certain, predetermined concentration of carbon.
  • the disadvantage of these alloys is that the dual-carbon system of carbon and iron loses very much ductility with increasing carbon content, without the corrosion resistance decreasing to the same extent.
  • an implant is known with a basic body which consists wholly or in part of a biocorrodible iron alloy.
  • the biocorrodible iron alloy has the formula Fe-P, wherein a proportion of P in the alloy 0.01 to 5 wt.% And Fe and production-related impurities occupy the remaining 100 wt.% Remaining amount of the alloy.
  • a disadvantage of the known alloy is that with increased P content, the ductility of the material decreases and thus it is less processable. However, the addition of P leads to an increase in the hardness of the material.
  • the Mn also mentioned in the document as an alloying ingredient serves as an aid for the precipitation of fine-phase Pd-containing intermetallic compounds, which are produced exclusively by the alloying of noble metals and / or heavy elements.
  • the use of precious metals or heavy metals is often problematic and costly.
  • an implantable body for intersomatic fusion made of a bioresorbable metallic material.
  • the metallic material has as its main component alkali metals, alkaline earth metals, iron, zinc or aluminum.
  • manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, rhenium, silicon, calcium, lithium, aluminum, zinc, carbon, sulfur, magnesium and / or iron are used.
  • the advantage of such a material is that the material has particularly favorable mechanical properties, in particular with regard to elasticity, deformability and stability at low mass. However, the degradation of the material is not yet in the desired time window.
  • US 2006/0229711 A1 concerns degradable medical devices.
  • US 2009/0017087 A1 discloses osseo-inductive metal implants.
  • US 2008/0281396 A1 describes medical devices such as guide wires and stents.
  • implants which consist of a biodegradable iron alloy are in the publications DE 197 31 021 A1 and WO 2007/082147 A2 disclosed.
  • the cited references describe iron alloys with nickel and chromium which, especially if they are not electropolished, release nickel ions.
  • the nickel ions not only lead to negative inflammatory effects in nickel allergy sufferers.
  • the degradation time is disadvantageously prolonged due to the formation of passivation layers.
  • the object of the present invention is to provide an implant which has a degradation of the implant in the desired target corridor, in particular in a shorter period, without a significant loss of ductility occurs.
  • the degradation should take place at a controllable time and also complicated shaped implants can be equipped with the desired degradation properties.
  • the object of the invention is also to provide a cost-effective method for producing such an implant.
  • an implant whose body has at least predominantly a material with the main component iron, wherein the material as the first secondary component sulfur with a concentration of more than 0.2 wt.% And at most 1 wt.%, Preferably at most 0 , 5 wt.%, Containing as second minor constituent at least one element of the group comprising calcium, manganese and magnesium, wherein the concentration of the second minor constituent calcium at least 0.1 wt.% And at most 1 wt.%, Preferably more than 0.2% by weight and at most 0.5% by weight, the concentration of the second secondary component manganese at least 0.5% by weight and at most 3% by weight, and / or the concentration of the second secondary component magnesium at least 0.3% by weight. % and at most 1% by weight, preferably at most 0.5% by weight.
  • the body of the implant comprises at least a part of the implant, preferably the main part of the implant, which effects the mechanical integrity of the implant.
  • microstructure is understood below to mean the arrangement of the constituents of solids (solids), in particular the arrangement of the crystallites (grains), pores, amorphous regions and grain boundary regions of the implant body.
  • alloying elements such as Mn, Mg and Ca in an Fe matrix of the microstructure serve as strong sulfide formers, which constitute internal local elements. Local elements accelerate the degradation process to about 1.5 times the degradation rate of the material, if it consists of stress-annealed pure iron.
  • the alloying elements mentioned can act in a preferred embodiment if they can be finely distributed during the melting process and the size of the particles can be limited.
  • the content of these alloying elements in the material according to the invention is advantageously selected such that, in conjunction with sulfur, they substantially reduce the corrosion resistance of the material, but the minimum requirements for mechanical properties imposed on a medical implant are met by the material , If the contents of said elements move beyond the stated ranges, either the degradation does not accelerate or the mechanical properties of the material (such as the elongation at break) are changed too much.
  • the content of heavy metals is limited to values ⁇ 1% by weight.
  • Another advantage of the implant according to the invention is that expensive surface treatment measures to accelerate the degradation behavior are no longer needed. However, these can optionally be considered supportive Measures for the acceleration of degradation are used. It is also advantageous that the material of the implant according to the invention does not cause any cytotoxic reactions in the body of the person treated, since, for example, nickel is not used as an alloying element.
  • the corrosion process can be better calculated, since there are no gradient layers and the corrosion process can be regarded as linear until self-dissolution.
  • the degradation runs through the entire volume of the material evenly.
  • the concentration of the second secondary component calcium is more than 0.2% by weight and at most 0.5% by weight and / or the concentration of the second secondary component magnesium is at most 0.5% by weight.
  • the material of the implant body additionally comprises chromium as secondary constituent, preferably with a concentration of 0.1% by weight to 1% by weight, particularly preferably with a concentration of 0.1% by weight to 0, 5% by weight.
  • the chromium-forming sulfides are also internal local elements. Chromium also contributes to the grain refining, so that on the one hand the degradation of the material on the one hand is further accelerated by the addition of chromium, on the other hand the mechanical properties of the material are favorably influenced by the effect of grain refining become. However, the content of chromium is not so high that it causes significant cell cell reactions due to the leaching out, if necessary with other heavy metals.
  • the main constituent of the material preferably contains more than 80% by weight, more preferably more than 90% by weight, of iron.
  • An iron-based alloy is particularly inexpensive to produce.
  • the material of the implant body additionally contains oxygen, preferably with a concentration of 0.05% by weight to 2% by weight, particularly preferably with a concentration of 0.05% by weight to 0.9 wt.%.
  • oxygen can cause the formation of oxide and oxisulfidischen particles in the structure of the material, which form further internal local elements to accelerate the degradation.
  • the material of the implant body additionally contains at least one element of the group which comprises carbon, phosphorus, vanadium, silicon, cerium, molybdenum, titanium, tungsten and zirconium.
  • the above alloying components further reduce the corrosion resistance of the material by forming further intermetallic compounds, while still meeting the minimum mechanical properties requirements imposed on the medical implant. This is due to the fact that the precipitates produced cause additional hardening of the material.
  • the addition of vanadium leads to the formation of strength-increasing and grain-refining vanadium carbides as well as the formation of vanadium oxides (vanadium (III) oxide, vanadium (V) oxide), which also contribute to corrosion acceleration.
  • Phosphorus in particular tends to microsegregate even at high cooling rates of the material during production. These microsections (zones with up to 4 wt.% Phosphorus) lead to an increased susceptibility to corrosion.
  • the concentration of carbon at least 0.1 wt.% And at most 0.5 wt.% Preferably at most 0.3 wt.%, And / or the concentration of phosphorus at least 0.05 wt.% And at most 0.5% by weight, preferably at most 0.3% by weight, and / or the concentration of vanadium is at least 0.1% by weight and at most 0.5% by weight, preferably at most 0.2% by weight, and / or the Concentration of silicon at least 0.05% by weight and at most 0.5% by weight, preferably at most 0.3% by weight, and / or the concentration of cerium at least 0.05% by weight and at most 0.5% by weight , preferably at most 0.3% by weight.
  • alloying constituents which form sulphidic and oxidic as well as oxisulfidic microparticles are chosen such that on the one hand they produce precipitation-hardening effects which lead to sufficiently high strength properties and thereby do not let the elongation at break drop below 15% due to grain refining effects likewise present.
  • the largest proportion of sulfide, oxide or Oxisulfid precipitates lies with its particle size in the submicrometer range (average diameter smaller than 1 micron).
  • the precipitates as dark spots (1 to 3 microns particle size) as Fe and Mn sulfides, oxysulfides or oxides microscopic in longitudinal and transverse sections after etching with 3% alcoholic nitric acid with a total surface area of all points of less than 3% of the surface of the respective cut visible.
  • the precipitates may be due to the previous deformation in a line-like preferred direction.
  • the dark coloration results from the higher corrosion potential of these precipitates or from holes that form due to dissolution of the particles during the etching process.
  • cylinders, hollow cylinders, plates, cuboids, hollow blocks or the like, in particular thin-walled tubes for stents can be produced.
  • the specified manufacturing process is very cost effective as it involves only a few steps.
  • the individual manufacturing steps are easy to control, so that the individual properties of the material or the implant can be easily adjusted.
  • the microstructural properties of the semifinished product or of the slab and thus also of the implant produced therefrom are essentially produced during the cooling of the melt; the hot forming step which may be necessary for the production of the semifinished product is at most of subordinate importance for the adjustment of the microstructural properties.
  • the cooling rate used in step b) is in the temperature range between 1200 ° C and 700 ° C at least 50 K / min and at most 100 K / min.
  • the primary solidification process which takes place during the pouring into the slab, and thus the existing cooling rate are determined primarily by the temperature of the melt, the temperature of the cold slab, the slab geometry and the melt volume.
  • the cooling conditions should be selected so that no pronounced segregation zones (segregations) occur. This means that the melt will remove the area between liquidus and solidus as quickly as possible, i. in a few seconds, should happen.
  • the subsequent cooling in the solid state should be carried out so fast that the temperature range between 1200 ° C and 700 ° C in a period of a maximum of 10 minutes is passed. This is usually given with a maximum slit diameter of 60 mm.
  • the cooling of the material from the melt takes place so rapidly that the particles produced do not agglomerate, but are distributed finely in the microstructure. This has a positive influence on the mechanical properties of the resulting implant, in particular, the elongation at break is not significantly reduced.
  • the slab can subsequently be processed by machining or turning off the surface or by deep hole drilling of a core. This procedure ensures that only homogeneous microstructure from the middle cross-section of the slab gets to further processing.
  • the optional, at least one hot working step mentioned above could include, for example, hot forging, intermediate annealing, or the like.
  • a tube is made from the slab by multi-step hot working above the recrystallization temperature. This is in the alloy according to the invention at a temperature above 550 ° C and preferably below 900 ° C. Due to the influence of temperature, the material does not undergo strain hardening, as at temperatures between 590 ° C and 630 ° C dynamic recrystallization always occurs. This leads to the formation of a recrystallization structure which, while having a low strength but also a high deformability. Subsequently, a deep hole drilling of the rod can be carried out at room temperature.
  • drawing steps at room temperature or at a temperature of up to 100 ° C.
  • an intermediate annealing at a temperature of 600 ° C. over a period of 30 minutes to 60 minutes can be carried out in air, which recrystallizes the microstructure and which restores the deformability of the material present before the drawing step.
  • a preferred embodiment of the method according to the invention comprises that between step b) and c) a stress relief annealing step is carried out, which preferably takes place in a temperature range from 570 ° C to 590 ° C, more preferably over a holding time of 30 minutes for a semifinished product in the mold a thin-walled pipe.
  • a stress relief annealing step preferably takes place in a temperature range from 570 ° C to 590 ° C, more preferably over a holding time of 30 minutes for a semifinished product in the mold a thin-walled pipe.
  • a stress relief annealing step a residue of strain hardening remains in the Material, thereby remaining residual stresses of the ferritic grid also favor the corrosion. Scaling is largely avoided.
  • step c) can alternatively or additionally include mechanical deburring, corundum blasting and / or pickling in mineral acid mixtures, for example in dilute nitric acid, so that the implant body acquires the desired geometry and is freed of production residues such as slag and burr ,
  • a coating for example a coating containing a pharmaceutically active substance or a coating which further accelerates the degradation, can be applied to an implant body produced in this way.
  • a "pharmaceutically active substance” (or therapeutically active or active substance) is understood to mean a plant, animal or synthetic active ingredient (medicament) or a hormone which, in suitable dosage, acts as a therapeutic agent for influencing states or functions of the body. as a substitute for naturally produced by the human or animal body active ingredients, such as insulin, as well as for the elimination or to make Harmful of pathogens, tumors, cancer cells or body foreign substances use.
  • the release of the substance in the vicinity of the implant has a positive effect on the healing process or counteracts pathological changes in the tissue as a result of the surgical procedure or serves to neutralize malady cells in oncology.
  • Such pharmaceutically active substances have, for example, an anti-inflammatory and / or antiproliferative and / or spasmolytic action, as a result of which, for example, restenoses, inflammations or (vascular) spasms can be avoided.
  • Such substances may be, for example, one or more substances of the active ingredient group of calcium channel blockers, lipid regulators (such as fibrates), immunosuppressants, calcineurin inhibitors (such as tacrolimus), antiflogistics (such as cortisone or dichlofenac), anti-inflammatory agents (such as imidazoles).
  • the antiallergic drugs such as dODN
  • the oligonucleotides such as dODN
  • estrogens such as genistein
  • endothelium formers such as fibrin
  • steroids proteins
  • hormones insulins
  • cytostatics peptides
  • vasodilators such as Sartane
  • antiproliferative agents the taxols or taxanes, here preferably paclitaxel or sirolimus (or its derivatives).
  • a melt of the abovementioned material composition is cast in slabs.
  • the slabs are cooled at an average cooling rate of 50 K / min. Cooling conditions are determined by the slab volume, the slab cross-section and by the ambient conditions (room temperature and air circulation).
  • the cooling conditions are such that the temperature range between 1200 ° C and 700 ° C is also passed through within the slab in the latest 3 hours.
  • the slab has a wall thickness of 600 mm, has an internal cross-section of 60 mm x 60 mm and a depth of 500 mm and consists of gray cast iron.
  • This volume of 1.8 dm 3 has a weight of about 14.0 kg.
  • this amount of steel in not additionally cooled slabs cools from 1200 ° C to 700 ° C within no more than 10 minutes. This corresponds to an average cooling rate of approx. 50 K / min. Thereafter, the demolding and it follows a multi-stage hot deformation.
  • bars with a final diameter of 25.4 mm are produced in several stages.
  • the multi-stage hot forming takes place above the recrystallization temperature. This is the case with the specified alloy at a temperature above 550 ° C and below 900 ° C. This means that first of all a rod with the outside diameter of about 25 mm and a length of 0.5 m is produced from the slab by hot forging. Due to the influence of temperature, this rod does not undergo strain hardening, as at temperatures between 590 ° C and 630 ° C always a dynamic recrystallization takes place. This leads to the formation of a recrystallization structure which, while having a low strength but also a high deformability.
  • the now existing tube is then pulled in about 20 drawing steps to the final geometry of 2.00 mm outside diameter with a wall thickness of 200 microns.
  • the technology of the pipe train with revolving rod is used.
  • the inner diameter of the drawn tube is formed over the outer diameter of a follower rod.
  • the length of the inserted rod must be at least equal to the length of the finished drawn pipe.
  • an intermediate annealing is carried out at a temperature of 600 ° C. for 30 minutes to 60 minutes in air.
  • the tube is detached from the rod by a rolling process and finally withdrawn.
  • the rod To weld between the moving rod and avoid the pipe inside diameter, the rod must be made of a different steel than the alloy of the invention. Best suited for this purpose is a high-alloy steel such as the 1.4841 with Cr, Ni and Si as main alloying elements.
  • the tube is annealed stress-relieved. This is done at a temperature between 570 ° C and 590 ° C for 30 min.
  • stent-like geometries are now cut by means of known laser cutting methods.
  • the final contour of these stents which is characterized by approximately square web cross-sections of about 100 .mu.m.times.100 .mu.m, is then produced by erosive methods such as pickling in acid mixtures, corundum blasting and electropolishing. As a result, production residues such as slag and burr are removed.
  • the length of a stent thus produced may be between 10 mm and 30 mm. However, stents for peripheral applications can be longer.
  • the structure of the stents thus produced is ferritic.
  • the ferrite grains also shares of a maximum of 30% perlite are present.
  • the mean grain size is about 25 microns. This corresponds to a particle size index of 8 according to ASTM.
  • the described material composition of the stent thus produced degrades about 1.5 times faster compared to pure iron with 99.5% iron content under body environment conditions. This means that a stent with a cross-section of 100 ⁇ m x 100 ⁇ m is completely degraded after about 18 months. A stent made of pure iron would be demoted completely only after 24 months.
  • Orthopedic implants such as angularly stable plates for the osteosynthesis of small fragments of the humerus are machined from a rod described above by milling and drilling.
  • the wall thicknesses are approx. 0.3 mm to 0.5 mm. Due to the relative robustness compared to stents this deburred by means of vibratory grinding.
  • An electropolishing can optionally be used for the purpose of further edge rounding.
  • An angle-stable plate for osteosynthesis is similar to that of the stent shown above. Depending on the specific geometry and location of implantation, such an angle-stable plate degrades in the period between 2 and 3 years. A plate made of pure iron, however, builds up completely after at least 4 years.
  • the stents and orthopedic implants shown above are to be rinsed immediately after the last wet-treatment step in isopropanol or acetone and blown dry by means of warm air. As a result, premature corrosion is avoided.

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  • Prostheses (AREA)

Claims (10)

  1. Implant, notamment endoprothèse intraluminale, dont le corps présente au moins principalement un matériau avec pour composant principal le fer, caractérisé en ce que le matériau contient en tant que premier composant secondaire du soufre avec une concentration supérieure à 0,2 % en poids et maximale de 1 % en poids, et en tant que deuxième composant secondaire au moins un élément du groupe, lequel comprend le calcium, le manganèse et le magnésium, où la concentration du deuxième composant secondaire calcium est d'au moins 0,1 % en poids et au maximum de 1 % en poids, la concentration du deuxième composant secondaire manganèse est d'au moins 0,5 % en poids et au maximum de 3 % en poids et/ou la concentration du deuxième composant secondaire magnésium est d'au moins 0,3 % en poids et au maximum de 1 % en poids.
  2. Implant selon la revendication 1, caractérisé en ce que la concentration du deuxième composant secondaire calcium est supérieure à 0,2 % en poids et au maximum de 0,5 % en poids et la concentration du deuxième composant secondaire magnésium est d'au moins 0,3 % en poids et au maximum de 0,5 % en poids.
  3. Implant selon l'une des revendications 1 à 2, caractérisé en ce que le matériau du corps d'implant présente en outre du chrome, de préférence avec une concentration de 0,1 % en poids à 1 % en poids, de manière particulièrement préférée avec une concentration de 0,1 % en poids à 0,5 % en poids.
  4. Implant selon l'une des revendications précédentes, caractérisé en ce que le matériau du corps d'implant présente principalement du fer, de préférence plus de 80 % en poids, de manière particulièrement préférée plus de 90 % en poids de fer.
  5. Implant selon l'une des revendications précédentes, caractérisé en ce que le matériau du corps d'implant présente en outre de l'oxygène, de préférence avec une concentration de 0,05 % en poids à 2 % en poids, de manière particulièrement préférée avec une concentration de 0,05 % en poids à 0,9 % en poids.
  6. Implant selon l'une des revendications précédentes, caractérisé en ce que le matériau du corps d'implant contient en outre au moins un élément du groupe, lequel comprend du carbone, du phosphore, du vanadium, du silicium, du cérium, du molybdène, du titane, du tungstène et du zirconium.
  7. Implant selon la revendication 6, caractérisé en ce que la concentration du carbone est d'au moins 0,1 % en poids et au maximum de 0,5 % en poids, de préférence au maximum de 0,3 % en poids et/ou la concentration du phosphore est d'au moins 0,05 % en poids et au maximum de 0,5 % en poids, de préférence au maximum de 0,3 % en poids, et/ou la concentration du vanadium est d'au moins 0,1 % en poids et au maximum de 0,5 % en poids, de préférence au maximum de 0,2 % en poids, et/ou la concentration du silicium est d'au moins 0,05 % en poids et au maximum de 0,5 % en poids, de préférence au maximum de 0,3 % en poids, et/ou la concentration du cérium est d'au moins 0,05 % en poids et au maximum de 0,5 % en poids, de préférence au maximum de 0,3 % en poids.
  8. Procédé de fabrication d'un implant, notamment une endoprothèse intraluminale, dont le corps présente au moins principalement un matériau avec pour constituant principal le fer, comprenant les étapes suivantes :
    a) fabrication d'un produit fondu avec une composition de matériau indiquée dans l'une des revendications précédentes,
    b) fabrication d'une brame par le refroidissement du produit fondu dans une forme correspondante selon une vitesse de refroidissement définie, prédéterminée et de préférence, exécution d'au moins une étape de formage à chaud pour la fabrication d'un produit semi-fini, où la vitesse de refroidissement utilisée se situe dans le domaine de température entre 1200 °C et 700 %°C à au moins 50 K/min et au maximum à 100 K/min.
    c) post-traitement du produit semi-fini ou de la brame, de préférence en utilisant le découpage ou laser jusqu'à la forme désirée du corps d'implant est fabriquée.
  9. Procédé selon la revendication 8, caractérisé en ce qu'entre l'étape b) et l'étape c), une étape de mise en température est réalisée, de préférence, dans un domaine de température de 570 °C à 590 °C, de manière particulièrement préférée sur une durée de maintien de 30 minutes pour un produit semi-fini sous la forme d'un tube à parois minces.
  10. Procédé selon l'une des revendications 8 ou 9, caractérisé en ce qu'après l'étape c), un revêtement, de préférence un revêtement contenant une substance pharmaceutiquement active, est rapporté sur le corps d'implant.
EP11168168.0A 2010-06-28 2011-05-31 Implant et son procédé de fabrication Not-in-force EP2399620B1 (fr)

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CN105686897B (zh) * 2014-11-28 2019-03-19 先健科技(深圳)有限公司 管腔支架与其预制件、管腔支架与其预制件的制备方法
CN104694848B (zh) * 2015-01-28 2017-03-29 燕山大学 一种生物可降解四元铁基合金材料及其制备方法
JP2020537050A (ja) * 2017-10-06 2020-12-17 バイオ ディージー， インコーポレイテッド 増大した分解速度を備えるｆｅ−ｍｎ吸収性インプラント合金
US10960110B2 (en) * 2018-08-21 2021-03-30 Jian Xie Iron-based biodegradable metals for implantable medical devices
CN116920180B (zh) * 2023-09-14 2023-12-15 乐普（北京）医疗器械股份有限公司 一种可降解金属材料及其制备方法与应用

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Publication number Priority date Publication date Assignee Title
EP3957339A1 (fr) 2020-08-19 2022-02-23 Leibniz-Institut für Festkörper- und Werkstoffforschung Dresden e.V. Matière implantaire et son utilisation
DE102020121729A1 (de) 2020-08-19 2022-02-24 Leibniz-Institut für Festkörper- und Werkstoffforschung Dresden e.V. (IFW Dresden e.V.) Implantatwerkstoff und dessen Verwendung
DE102020121729B4 (de) 2020-08-19 2023-11-02 Leibniz-Institut für Festkörper- und Werkstoffforschung Dresden e.V. (IFW Dresden e.V.) Implantatwerkstoff und dessen Verwendung

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EP2399620A3 (fr) 2014-09-03
US9480779B2 (en) 2016-11-01
EP2399620A2 (fr) 2011-12-28
US20170021062A1 (en) 2017-01-26
US20110318219A1 (en) 2011-12-29

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